Use of Non-Vitamin K Dependent Oral Anticoagulant in Ischemic Stroke

Atrial fibrillation (AF) is associated with an increased incidence of ischemic stroke and transient ischemic attack. A confluence of various factors such as blood stasis, endothelial dysfunction, and prothrombotic state could be contributing to the thrombogenesis in AF. Anticoagulation is the first-line therapy for the prevention of thromboembolism by AF. In current days, non-vitamin K dependent oral anticoagulants (NOAC) are considered as the preferred choice of anticoagulants to prevent ischemic stroke in patients with AF. NOACs have comparable good efficacy and better safety with a predictable anticoagulant effect without the routine coagulation monitoring compared to vitamin K dependent oral anticoagulant. However, the proper use of NOACs needs a careful approach to many practical aspects for balancing the preventing thromboembolic events and bleeding risk. Thus, understanding the drug metabolism and indication of NOAC for a specific situation is essential. In this article, we review major clinical trials, the mechanism, and the use of NOACs in the actual clinical setting of managing ischemic stroke patients.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Care Process of Recanalization Therapy for Acute Stroke during the COVID-19 Outbreak in South Korea

Background@#and Purpose We aimed to determine whether the care process and outcomes in patients with acute stroke who received recanalization therapy changed during the outbreak of coronavirus disease 2019 (COVID-19) in South Korea. @*Methods@#We used data from a prospective multicenter reperfusion therapy registry to compare the care process including the time from symptom onset to treatment, number of treated patients, and discharge disposition and treatment outcomes between before and during the COVID-19 outbreak in South Korea. @*Results@#Upon the COVID-19 outbreak in South Korea, the number of patients receiving endovascular treatment to decrease temporarily but considerably. The use of emergency medical services by stroke patients increased from 91.5% before to 100.0% during the COVID-19 outbreak (p=0.025), as did the median time from symptom onset to hospital visit [median (interquartile range), 91.0 minutes (39.8–277.0) vs. 176.0 minutes (56.0–391.5), p=0.029]. Furthermore, more functionally dependent patients with disabilities were discharged home (59.5% vs. 26.1%, p=0.020) rather than staying in a regional or rehabilitation hospital. In contrast, there were no COVID-19-related changes in the times from the hospital visit to brain imaging and treatment or in the functional outcome, successful recanalization rate, or rate of symptomatic intracerebral hemorrhage. @*Conclusions@#These findings suggest that a prehospital delay occurred during the COVID-19 outbreak, and that patients with acute stroke might have been reluctant to visit and stay in hospitals. Our findings indicate that attention should be paid to prehospital care and the behavior of patients with acute stroke during the COVID-19 outbreak.

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis / 대한뇌졸중학회지

Background@#and Purpose Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known. @*Methods@#We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up. @*Results@#Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P @*Conclusions@#NBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.

Clinical Impact of Intracerebral Hemorrhage after Hyperacute Extracranial Stenting in Patients with Ischemic Stroke / 신경중재치료의학

PURPOSE: Emergent intracranial occlusions causing acute ischemic stroke are often related to extracranial atherosclerotic stenosis. This study aimed to investigate the association between post-procedure intracerebral hemorrhage (ICH) and emergent extracranial artery stenting and assess their effects on clinical outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed patients undergoing hyperacute endovascular treatment for cervicocephalic vascular occlusion in three Korean hospitals between January 2011 and February 2016. Patients who had extracranial artery involvement and were treated from 24 hours of symptom onset to puncture were included in this study, and they were divided into the extracranial stenting (ES) and non-ES groups. Any type of petechial hemorrhages and parenchymal hematoma was defined as ICH for the current study. RESULTS: In total, 76 patients were included in this study. Among them, 56 patients underwent ES, and 20 patients did not. Baseline characteristics, risk factors, laboratory data, treatment methods, successful reperfusion rates, and baseline stenotic degrees of extracranial internal carotid artery did not differ between these two groups. However, atrial fibrillation was more frequent in patients without than with ES (P=0.002), and post-procedure ICH was more frequent in patients with than without ES (P=0.035). Logistic regression models revealed that ES was independently associated with post-procedure ICH (odds ratio [OR], 7.807; 95% confidence interval [CI], 1.213–50.248; P=0.031), and ICH was independently associated with poor clinical outcomes (OR, 0.202; 95% CI, 0.054–0.759; P=0.018); however, ES itself was not associated with clinical outcomes (OR, 0.530; 95% CI, 0.117–2.395; P=0.409). Notably, ICH and ES had interaction for predicting good outcomes (P=0.041). CONCLUSION: Post-procedure ICH was associated with ES and poor clinical outcomes. Therefore, ES should be cautiously considered in patients with hyperacute stroke.

Successful Endovascular Thrombectomy in a Patient with Monocular Blindness Due to Thrombus of the Ophthalmic Artery Orifice

BACKGROUND: Retinal artery occlusion can lead to sudden visual loss without pain. The acute management of retinal artery occlusion remains unresolved. CASE REPORT: A 65-year-old male was hospitalized to an emergency room for visual loss on the left side within 6 hours of onset. Combined occlusion at retinal artery and ciliary artery was confirmed by an ophthalmologist and we assessed ophthalmic artery occlusion. However, MRA revealed no significant steno-occlusion of internal carotid artery. Transfemoral cerebral angiography was carried out immediately and showed a movable thrombus at the orifice of the ophthalmic artery. We decided on endovascular thrombectomy to prevent permanent visual loss. Finally, his visual acuity was improved after successful thrombectomy. CONCLUSIONS: Although MRA is intact, small thrombus right at the orifice of the ophthalmic artery can cause a sudden monocular visual loss due to occlusion of the retinal artery. In this setting, urgent endovascular thrombectomy can offer visual improvement.

Infarct Core Expansion on Computed Tomography before and after Intravenous Thrombolysis

PURPOSE: Infarct core can expand rapidly in acute stroke patients receiving intravenous tissue plasminogen activator (IV t-PA). We investigated changes in the extent of infarct core during IV t-PA treatment, and explored the associative factors of this infarct core expansion in patients with proximal artery occlusion. MATERIALS AND METHODS: We included patients who were considered for sequential intra-arterial therapy (IAT) due to occlusion of intracranial proximal artery after IV t-PA. Patients who had a baseline Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) ≥6 and who underwent two consecutive CT scans before and shortly after IV t-PA infusion were enrolled. Patients were classified into no, moderate, and marked expansion groups based on decreases in ASPECTS (0–1, 2–3, and ≥4, respectively) on follow-up CT. Collateral status was graded using CT angiography. RESULTS: Of the 104 patients, 16 (15.4%) patients showed moderate and 13 (12.5%) patients showed marked infarct core expansion on follow-up CT scans obtained at 71.1±19.1 min after baseline CT scan. Sixteen (15.4%) patients had an ASPECTS value < 6 on the follow-up CT. None of the patients with marked expansion were independent at 3 months. Univariate analysis and ordinal logistic regression analysis demonstrated that the infarct core expansion was significantly associated with collateral status (p < 0.001). CONCLUSION: Among patients who were considered for IAT after IV t-PA treatment, one out of every seven patients exhibited marked expansion of infarct core on follow-up CT before IAT. These patients tend to have poor collaterals and poor outcomes despite rescue IAT.

Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke

BACKGROUND AND PURPOSE: The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. METHODS: In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. RESULTS: CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07–1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01–1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30–3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82–1.67). CONCLUSIONS: The total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.

Increased Risk of Cardiovascular Events in Stroke Patients Who had Not Undergone Evaluation for Coronary Artery Disease

PURPOSE: Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. MATERIALS AND METHODS: This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (−) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. RESULTS: During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (−) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (−) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172–8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (−) group seemed to also have a higher risk of recurrent stroke. CONCLUSION: Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.

Computed Tomography-Based Thrombus Imaging for the Prediction of Recanalization after Reperfusion Therapy in Stroke / 대한뇌졸중학회지

The prediction of successful recanalization following thrombolytic or endovascular treatment may be helpful to determine the strategy of recanalization treatment in acute stroke. Thrombus can be detected using noncontrast computed tomography (CT) as a hyperdense artery sign or blooming artifact on a T2*-weighted gradient-recalled image. The detection of thrombus using CT depends on slice thickness. Thrombus burden can be determined in terms of the length, volume, and clot burden score. The thrombus size can be quantitatively measured on thin-section CT or CT angiography/magnetic resonance angiography. The determination of thrombus size may be predictive of successful recanalization/non-recanalization after intravenous thrombolysis and endovascular treatment. However, cut-offs of thrombus size for predicting recanalization/non-recanalization are different among studies, due to different methods of measurements. Thus, a standardized method to measure the thrombus is necessary for thrombus imaging to be useful and reliable in clinical practice. Software-based measurements may provide a reliable and accurate assessment. The measurement should be easy and rapid to be more widely used in practice, which could be achieved by improvement of the user interface. In addition to prediction of recanalization, sequential measurements of thrombus volume before and after the treatment may also be useful to determine the efficacy of new thrombolytic drugs. This manuscript reviews the diagnosis of thrombus, prediction of recanalization using thrombus imaging, and practical considerations for the measurement of thrombus burden and density on CT.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2+/-1.0 mm3 vs. placebo: 0.3+/-1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2+/-1.0 mm3 vs. placebo: 0.3+/-1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Decision-Making Support Using a Standardized Script and Visual Decision Aid to Reduce Door-to-Needle Time in Stroke / 대한뇌졸중학회지

No abstract available.

Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients with Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. METHODS: We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. RESULTS: AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). CONCLUSIONS: In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.